RPE specification in the chick is mediated by surface ectoderm-derived BMP and Wnt signalling

Steinfeld, Jörg; Steinfeld, Ichie; Coronato, Nicola; Hampel, Meggi-Lee; Layer, Paul G.; Araki, Masasuke; Vogel‐Höpker, Astrid

doi:10.1242/dev.096990

Cited by 63 publications

(76 citation statements)

References 82 publications

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“…Interestingly, BMP signaling was autonomously activated within mESC-derived neuroepithelium. This observation provides a novel view for induction of BMP signaling, which has been reported to be activated through interaction between optic vesicle and surface ectoderm in mouse and chick embryos (Furuta and Hogan, 1998;Trousse et al, 2001;Muller et al, 2007;Behesti et al, 2006;Steinfeld et al, 2013).…”

Section: Bmp Signaling Directly Regulates D-v Polarization and Invagimentioning

confidence: 81%

“…In the developing eye, the optic cup is exposed to these external cues from surrounding non-retinal tissues such as periocular mesenchyme, diencephalic neuroepithelium and surface ectoderm (Furuta and Hogan, 1998;Fuhrmann et al, 2000;Kobayashi et al, 2010;Steinfeld et al, 2013). However, in our ESC culture, interactions with these tissues are absent.…”

Section: Endogenous Bmp Signaling Regulates D-v Specification In Mescmentioning

confidence: 90%

“…Wnt signaling is also known to be involved in D-V polarization of retinal tissue (Veien et al, 2008;Hägglund et al, 2013). Wnt2b (Wnt13) is localized in dorsal RPE at an early optic vesicle stage in mice and chicks (Cho and Cepko, 2006;Steinfeld et al, 2013). In mice deficient in the Wnt receptor or its downstream component, dorsal retinal markers such as Bmp4 and Tbx5 are diminished (Zhou et al, 2008;Esteve et al, 2011;Hägglund et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Emergence of dorsal-ventral polarity in ES cell-derived retinal tissue

Hasegawa¹,

Takata²,

Okuda³

et al. 2016

Development

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We previously demonstrated that mouse embryonic stem cell (mESC)-derived retinal epithelium self-forms an optic cup-like structure. In the developing retina, the dorsal and ventral sides differ in terms of local gene expression and morphological features. This aspect has not yet been shown in vitro. Here, we demonstrate that mESC-derived retinal tissue spontaneously acquires polarity reminiscent of the dorsal-ventral (D-V) patterning of the embryonic retina. Tbx5 and Vax2 were expressed in a mutually exclusive manner, as seen in vivo. Three-dimensional morphometric analysis showed that the in vitro-formed optic cup often contains cleft structures resembling the embryonic optic fissure. To elucidate the mechanisms underlying the spontaneous D-V polarization of mESCderived retina, we examined the effects of patterning factors, and found that endogenous BMP signaling plays a predominant role in the dorsal specification. Further analysis revealed that canonical Wnt signaling, which was spontaneously activated at the proximal region, acts upstream of BMP signaling for dorsal specification. These observations suggest that D-V polarity could be established within the self-formed retinal neuroepithelium by intrinsic mechanisms involving the spatiotemporal regulation of canonical Wnt and BMP signals.

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Section: Bmp Signaling Directly Regulates D-v Polarization and Invagimentioning

confidence: 81%

Section: Endogenous Bmp Signaling Regulates D-v Specification In Mescmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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Emergence of dorsal-ventral polarity in ES cell-derived retinal tissue

Hasegawa¹,

Takata²,

Okuda³

et al. 2016

Development

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“…Previous findings demonstrated that Wnt/GSK3β signals through the stabilization of BMP/Smad during cell fate specification, both in neuroepidermal patterning (25) and, more recently, the induction of the retinal pigment epithelium (45). Future experiments will need to determine whether and how these pathways act to coordinate cell migration with cell fate specification.…”

Section: Discussionmentioning

confidence: 99%

Smad1 transcription factor integrates BMP2 and Wnt3a signals in migrating cardiac progenitor cells

Song

McColl

Camp

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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In vertebrate embryos, cardiac progenitor cells (CPCs) undergo long-range migration after emerging from the primitive streak during gastrulation. Together with other mesoderm progenitors, they migrate laterally and then toward the ventral midline, where they form the heart. Signals controlling the migration of different progenitor cell populations during gastrulation are poorly understood. Several pathways are involved in the epithelialto-mesenchymal transition and ingression of mesoderm cells through the primitive streak, including fibroblast growth factors and wingless-type family members (Wnt). Here we focus on early CPC migration and use live video microscopy in chicken embryos to demonstrate a role for bone morphogenetic protein (BMP)/SMA and MAD related (Smad) signaling. We identify an interaction of BMP and Wnt/glycogen synthase kinase 3 beta (GSK3β) pathways via the differential phosphorylation of Smad1. Increased BMP2 activity altered migration trajectories of prospective cardiac cells and resulted in their lateral displacement and ectopic differentiation, as they failed to reach the ventral midline. Constitutively active BMP receptors or constitutively active Smad1 mimicked this phenotype, suggesting a cell autonomous response. Expression of GSK3β, which promotes the turnover of active Smad1, rescued the BMP-induced migration phenotype. Conversely, expression of GSK3β-resistant Smad1 resulted in aberrant CPC migration trajectories. Derepression of GSK3β by dominant negative Wnt3a restored normal migration patterns in the presence of high BMP activity. The data indicate the convergence of BMP and Wnt pathways on Smad1 during the early migration of prospective cardiac cells. Overall, we reveal molecular mechanisms that contribute to the emerging paradigm of signaling pathway integration in embryo development.live imaging | cell tracking

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“…Wnt activity is not required or sufficient to specify neural retina cells, but a combination of Wnt and BMP signals induces RPE cells Wnt signals have been suggested to be important for the generation of RPE cells (Fujimura et al, 2009;Steinfeld et al, 2013), but whether Wnt activity plays any role in the specification of neural retina cells has not been determined. We therefore first tested whether Wnt activity is required for the specification of neural retina cells, by culturing stage 10 OVL explants and stage 13 OV explants together with a soluble Frizzled receptor (Frizzled-conditioned medium) to inhibit Wnt activity (Gunhaga et al, 2003;Hsieh et al, 1999).…”

Section: Direct Requirement Of Bmp Activity For the Specification Of mentioning

confidence: 99%

Neural retina identity is specified by lens‐derived BMP signals

Gunhaga

Pandit

Patthey

et al. 2017

Acta Ophthalmologica

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The eye has served as a classical model to study cell specification and tissue induction for over a century. Nevertheless, the molecular mechanisms that regulate the induction and maintenance of eye-field cells, and the specification of neural retina cells are poorly understood. Moreover, within the developing anterior forebrain, how prospective eye and telencephalic cells are differentially specified is not well defined. In the present study, we have analyzed these issues by manipulating signaling pathways in intact chick embryo and explant assays. Our results provide evidence that at blastula stages, BMP signals inhibit the acquisition of eye-field character, but from neural tube/optic vesicle stages, BMP signals from the lens are crucial for the maintenance of eye-field character, inhibition of dorsal telencephalic cell identity and specification of neural retina cells. Subsequently, our results provide evidence that a Rax2-positive eyefield state is not sufficient for the progress to a neural retina identity, but requires BMP signals. In addition, our results argue against any essential role of Wnt or FGF signals during the specification of neural retina cells, but provide evidence that Wnt signals together with BMP activity are sufficient to induce cells of retinal pigment epithelial character. We conclude that BMP activity emanating from the lens ectoderm maintains eye-field identity, inhibits telencephalic character and induces neural retina cells. Our findings link the requirement of the lens ectoderm for neural retina specification with the molecular mechanism by which cells in the forebrain become specified as neural retina by BMP activity.

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RPE specification in the chick is mediated by surface ectoderm-derived BMP and Wnt signalling

Cited by 63 publications

References 82 publications

Emergence of dorsal-ventral polarity in ES cell-derived retinal tissue

Emergence of dorsal-ventral polarity in ES cell-derived retinal tissue

Smad1 transcription factor integrates BMP2 and Wnt3a signals in migrating cardiac progenitor cells

Neural retina identity is specified by lens‐derived BMP signals

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